Effects Of Tibial Nerve Stimulation Research Articles

Effects of motor stimulation of the tibial nerve on corticospinal excitability of abductor hallucis and pelvic floor muscles.

Peripheral nerve stimulation can modulate the excitability of corticospinal pathways of muscles in the upper and lower limbs. Further, the pattern of peripheral nerve stimulation (continuous vs. intermittent) may be an important factor determining the modulation of this corticospinal excitability. The pelvic floor muscles (PFM) are crucial for maintaining urinary continence in humans, and share spinal segmental innervation with the tibial nerve. We explored the idea of whether the neuromodulatory effects of tibial nerve stimulation (TibNS) could induce effects on somatic pathways to the PFM. We evaluated the effects of two patterns of stimulation (intermittent vs. continuous) on corticospinal excitability of the PFM compared to its effect on the abductor hallucis (AH) muscle (which is directly innervated by the tibial nerve). We hypothesized that intermittent TibNS would increase, while continuous stimulation would decrease, the excitability of both AH and PFM. Twenty able-bodied adults (20-33 years of age) enrolled in this study. TibNS was delivered either intermittently (1 ms pulses delivered at 30Hz with an on:off duty cycle of 600:400 ms, for 60 min), or continuously (1 ms pulses delivered at 30Hz for 36 min) just above the motor threshold of the AH. We randomized the order of the stimulation pattern and tested them on separate days. We used surface electromyography (EMG) to record motor-evoked responses (MEP) in the PFM and AH following transcranial magnetic stimulation (TMS). We generated stimulus-response (SR) curves to quantify the changes in peak-to-peak MEP amplitude relative to TMS intensity to assess changes in corticospinal excitability pre- and post-stimulation. We found that TibNS increased corticospinal excitability only to AH, with no effects in PFM. There was no difference in responses to continuous vs. intermittent stimulation. Our results indicate a lack of effect of TibNS on descending somatic pathways to the PFM, but further investigation is required to explore other stimulation parameters and whether neuromodulatory effects may be spinal in origin.

Immediate and Long-Term Effects of Tibial Nerve Stimulation on the Sexual Behavior of Female Rats

ObjectivesThere are limited treatment options for female sexual dysfunction (FSD). Percutaneous tibial nerve stimulation (PTNS) has shown improvements in FSD symptoms in neuromodulation clinical studies, but the direct effects on sexual function are not understood. This study evaluated the immediate and long-term effects of PTNS on sexual motivation and receptivity in a rat model of menopausal women. Our primary hypothesis was that long-term PTNS would yield greater changes in sexual behavior than short-term stimulation. Materials and MethodsIn two experiments, after receiving treatment, we placed ovariectomized female rats in an operant chamber in which the female controls access to a male by nose poking. We used five treatment conditions, which were with or without PTNS and no, partial, or full hormone priming. In experiment 1, we rotated rats through each condition twice with behavioral testing immediately following treatment for ten weeks. In experiment 2, we committed rats to one condition for six weeks and tracked sexual behavior over time. We quantified sexual motivation and sexual receptivity with standard measures. ResultsNo primary comparisons were significant in this study. In experiment 1, we observed increased sexual motivation but not receptivity immediately following PTNS with partial hormone priming, as compared with priming without PTNS (linear mixed effect models; initial latency [p = 0.34], inter-interval latency [p = 0.77], nose poke frequency [p = 0.084]; eight rats). In experiment 2, we observed trends of increased sexual receptivity (linear correlation for weekly group means; mounts [p = 0.094 for trendline], intromissions [p = 0.073], lordosis quotient [p = 0.58], percent time spent with a male [p = 0.39], decreased percent time alone [p = 0.024]; four rats per condition), and some sexual motivation metrics (linear correlation for weekly group means; nose pokes per interval [p = 0.050], nose poke frequency [p = 0.039], decreased initial latency [p = 0.11]; four rats per condition) when PTNS was applied long-term with partial hormone priming, as compared with hormone-primed rats without stimulation. ConclusionsPTNS combined with hormone priming shows potential for increasing sexual motivation in the short-term and sexual receptivity in the long-term in rats. Further studies are needed to examine variability in rat behavior and to investigate PTNS as a treatment for FSD in menopausal women.

Inhibitory effects of a smartphone-controlled wearable transcutaneous tibial nerve stimulation device on bladder reflexes in anesthetized cats.

To explore the inhibitory effects of a novel, smartphone-controlled, and wearable tibial nerve stimulation device on nonnociceptive and nociceptive bladder reflexes in anesthetized cats and to compare the stimulus results of two current waveforms outputted by this new stimulator. A novel, intelligent tibial nerve stimulator was put on the ankles of 14 cats and controlled by a mobile application. Cystometrograms (CMGs) were performed repeatedly by infusing 0.9% normal saline (NS) and 0.5% acetic acid (AA) through a urethral catheter. Inhibitory effects were explored by measuring the bladder capacity (BC) in two areas: (1) on nonnociceptive bladder reflex (infused with NS) and on nociceptive bladder reflex (filled with AA to induce overactive bladder [OAB] model); and (2) under the stimulation of two different current waveforms (waveforms A and B). In Group 1, the BC of AA-induced OAB (41.48 ± 8.40%) was significantly different compared with the capacity of a NS-infused bladder (104.89 ± 1.32%, p < 0.05). Both NS-filled (151.35 ± 5.71%, p < 0.05) and AA-instilled (71.41 ± 9.34%, p < 0.05) bladder volumes significantly increased after tibial nerve stimulation (TNS). In Group 2, the BC increased to 166.18 ± 15.17% (p = 0.026) and 127.64 ± 13.00% (p = 0.239), respectively, after TNS with waveforms A and B current. Results revealed that this novel, smartphone-based, wearable, and wireless tibial nerve stimulation system could inhibit the micturition reflex on physiological condition, serving as a potential option for OAB treatment. In addition, the waveforms of stimulation current had an important influence on the effects of TNS.

Optimized Tibial Nerve Stimulation Partially Reduces Visceral Hypersensitivity in Rats Mediated via Autonomic and Opioid Mechanisms

The aim of this study was to investigate the therapeutic effect and possible mechanisms of tibial nerve stimulation (TNS) on visceral hypersensitivity in rats. 1) The effects of TNS with five sets of parameters on visceral sensitivity in normal rats were evaluated by the assessment of abdominal electromyogram (EMG) and abdominal withdrawal reflex (AWR). 2) The effects and mechanisms of TNS with a special set of parameters (14Hz, 330 μsec, and 40% motor threshold) were evaluated in acute visceral hypersensitivity rats induced by restraint stress and colonic hypersensitized rats induced by acetic acid during the neonatal stage assessed by the EMG, AWR, and the spectral analysis of heart rate variability derived from the electrocardiogram. 1) In normal rats, TNS did not show any effect on the visceromotor reflex. 2) In rats with restraint stress-induced hypersensitivity, TNS with the special set of parameters reduced AWR scores and EMG responses to rectal distention at a pressure of 20-60 mmHg (p < 0.05, vs. baseline for both AWR and EMG). Concurrently, TNS increased vagal activity and decreased sympathetic activity (p < 0.03 for both). 3) Similar effects were noted on the EMG (p < 0.05, vs. baseline) and AWR (p < 0.05 vs. baseline) with acute and chronic TNS in rats with chronic colonic hypersensitivity and the effects were blocked by naloxone. TNS with parameters of 14Hz, 330 μsec, and 40% motor threshold is effective in improving visceral hypersensitivity in rodent models of colonic hypersensitivity via the modulation of autonomic and opioid mechanisms.

Inhibitory effects of a minimally invasive implanted tibial nerve stimulation device on non-nociceptive bladder reflexes in cats.

The present study investigated the inhibitory effects of a novel minimally invasive implanted tibial nerve stimulation device on non-nociceptive bladder reflexes in cats. A wireless minimally invasive implanted nerve stimulator was implanted adjacent to the left tibial nerve in seven cats. Multiple cystometrograms (CMGs) were obtained to determine the inhibitory effects of tibial nerve stimulation (TNS) at different frequencies and intensities on the micturition reflex by infusing normal saline (NS). TNS at 6Hz did not significantly change the bladder capacity (BC) compared to the control level at the intensity threshold (T), while TNS significantly (P < 0.05) increased the BC to 158.89 ± 20.57% of the control level at 2T. When stimulated at 15Hz, TNS did not significantly (P > 0.05) change the BCs at 1T and 2T. The minimally invasive implanted TNS device was shown to be effective in inhibiting the micturition reflex under physiologic conditions. Further studies are warranted to determine the inhibitory effects of TNS on nociceptive bladder reflexes.

Effect of Tibial Nerve Stimulation on Menopause‐associated Symptoms in Ovariectomized Rats

Human menopause transition and post‐menopausal syndrome, driven by reduced ovarian activity which reduces estrogen levels, are associated with an increased risk for symptoms including but not limited to sexual dysfunction, osteoporosis, and metabolic disease. Current treatments (both hormonal and non‐hormonal) are limited in efficacy and may have adverse consequences, so investigation for additional treatment options are necessary. Previous studies have demonstrated that tibial nerve stimulation or electro‐acupuncture are minimally invasive treatments that increase vaginal blood flow and serum estrogen in the rat model. In this study we examined the effects of biweekly tibial nerve stimulation (0.2 ms pulse width, 20 Hz, 2× motor threshold) under ketamine‐xylazine anesthesia in female ovariectomized (OVX) Sprague Dawley rats on various measurements that can change in association with menopause (serum estradiol, resting blood glucose, vaginal blood perfusion, uterine weight/histology, and bone density) either at weekly time‐points or during a terminal necropsy. Rats were split into three groups (n = 10 per group): 1) intact + no stimulation, 2) OVX + no stimulation, and 3) OVX + stimulation. Although preliminary data has not shown significant differences between treatment groups, data collection is ongoing and trends are expected after weeks of stimulation. The results of this study will examine the effects of tibial nerve stimulation on various menopause associated symptoms, and help guide recommendations for future studies and treatments.

537 - Inhibitory effect of tibial nerve stimulation on the micturition reflex in the rat

537 - Inhibitory effect of tibial nerve stimulation on the micturition reflex in the rat

Tibial Nerve Stimulation to Drive Genital Sexual Arousal in an Anesthetized Female Rat

BackgroundThere is clinical evidence that percutaneous tibial nerve stimulation can positively benefit women with female sexual interest/arousal disorder, yet no studies have explored the potential mechanisms further. AimTo investigate the effect of tibial nerve stimulation on vaginal blood perfusion (VBP) in an anesthetized rat model. Methods16 ketamine-anesthetized rats were surgically implanted with a nerve cuff electrode on 1 tibial nerve. The tibial nerve was stimulated for 30 minutes continuously or non-continuously at a frequency of 10 to 25 Hz. OutcomesVBP was measured with laser Doppler flowmetry and analyzed using a wavelet transform of time-frequency representations with a focus on the neurogenic energy range (0.076–0.200 Hz). Results25 of 33 (75.8%) stimulation periods had at least a 500% increase in laser Doppler flowmetry neurogenic energy compared with baseline. This increase was most common within 20 to 35 minutes after the start of stimulation. There was no statistically significant difference for frequency used or estrous cycle stage. Clinical TranslationThe results of this study provide further support for percutaneous tibial nerve stimulation as an alternative treatment option for women with genital arousal aspects of female sexual interest/arousal disorder. Strengths and LimitationsThis study successfully demonstrates the ability of tibial nerve stimulation to increase VBP. However, further studies to determine parameter optimization and to illuminate neural mechanisms are needed. Further studies also are necessary to determine effects of repeated stimulation sessions. ConclusionLong-duration tibial stimulation was successful at driving increases in the neurogenic component of VBP, providing evidence that tibial nerve stimulation could be used to treat genital arousal aspects of female sexual interest/arousal disorder by improving pelvic blood flow.Zimmerman LL, Rice IC, Berger MB, Bruns TM. Tibial Nerve Stimulation to Drive Genital Sexual Arousal in an Anesthetized Female Rat. J Sex Med 2018;15:296–303.

Inhibitory effects of tibial nerve stimulation on bladder neurophysiology in rats.

Tibial nerve stimulation (TNS) is a form of peripheral neuromodulation which has been found effective in treating overactive bladder symptoms, with lesser side effects than first line pharmacotherapy. Despite its widespread clinical use, the underlying mechanism of action is not fully understood. Our aim was to study its effect on the bladder neurophysiology and the trigger mechanism of voiding in the overactive detrusor, simulated by acetic acid (AA) instillation. In urethane anaesthetized male Wistar rats, the tibial nerve was stimulated for 30 min at 5 Hz, pulse width 200 µs and amplitude approximately three times the threshold to induce a slight toe movement. The pressure at which a voiding contraction was triggered (pthres) did not change significantly between the pre- and post-TNS measurements in AA induced detrusor overactivity. It was found that TNS significantly reversed the effects of AA irritation by increasing the bladder compliance and the bladder volume at pthres, as well as suppressed the threshold afferent nerve activity. The slope of the linear relationship between pressure and the afferent activity increased after AA instillation and decreased significantly after stimulation. In addition to its well-known central inhibitory mechanisms, this study has demonstrated that TNS improves bladder storage capacity by delaying the onset of voiding, via an inhibitory effect on the bladder afferent signaling at the peripheral level.

Effect of tibial nerve stimulation on bladder afferent nerve activity in a rat detrusor overactivity model.

To study the post-stimulation effect of tibial nerve stimulation on rat bladder afferent activity, and urodynamic parameters in normal and acetic acid-induced detrusor overactivity conditions. In urethane anesthetized male Wistar rats, the tibial nerve was stimulated for 30 min at 5 Hz, pulse width 200 μs and amplitude approximately threefold the threshold to induce a slight toe movement. The post-stimulation effect was studied by measuring afferent nerve activity of postganglionic pelvic nerve branches and various urodynamic parameters under two different conditions: (i) in physiological saline filling experiments (simulating normal bladder condition); and (ii) in acetic acid irritated bladders (simulating detrusor overactivity). After 30 min of tibial nerve stimulation in saline filling experiments, the bladder capacity, threshold pressure and afferent nerve activity were not significantly different from the prestimulation measurements. The instillation of 0.5% acetic acid significantly reduced the bladder capacity and increased the afferent nerve activity. Tibial nerve stimulation significantly improved the bladder capacity and suppressed the afferent nerve activity compared with prestimulation acetic acid measurements. Tibial nerve stimulation is able to significantly restore the bladder capacity by inhibiting afferent nerve activity in chemically irritated rat bladders. The present study provides important basic electrophysiological evidence to substantiate the clinical use of tibial nerve stimulation for treatment of symptoms related to detrusor overactivity.

Poststimulation inhibition of the micturition reflex induced by tibial nerve stimulation in rats.

The purpose of this study was to determine the effect of tibial nerve stimulation (TNS) on the micturition reflex. Experiments were conducted in 24 rats under urethane anesthesia. A catheter was inserted into the bladder via the bladder dome for saline infusion. A cuff electrode was placed around right tibial nerve for stimulation. TNS (5 Hz, 0.2 msec pulse width) at 2–4 times the threshold (T) intensity for inducing a toe movement was applied either during slow (0.08 mL/min) infusion of the bladder or for 30 min with an empty bladder. TNS had no effect on the micturition reflex when it was applied during slow bladder infusion. However, the 30‐min TNS applied with an empty bladder induced poststimulation inhibition and significantly (P < 0.05) increased the bladder capacity to about 140% of prestimulation level in a 50‐min period following the termination of stimulation. The bladder compliance was also significantly (P < 0.05) increased after the 30‐min TNS. These results suggest that different mechanisms might exist in acute‐ and post‐TNS inhibition of micturition reflex. The animal model developed in this study will be very useful for further investigations of the neurotransmitter mechanisms underlying tibial neuromodulation of bladder function.

Irritation Induced Bladder Overactivity is Suppressed by Tibial Nerve Stimulation in Cats

We investigated the effects of tibial nerve stimulation on bladder overactivity induced by acetic acid irritation. Cystometry was performed in 10 α-chloralose anesthetized female cats by infusing saline or acetic acid through a urethral catheter that was secured by a ligature around the urethra. Intravesical infusion of 0.25% acetic acid was used to irritate the bladder and induce bladder overactivity. Multiple cystometrograms were done before, during and after tibial nerve stimulation to determine the inhibitory effect on the micturition reflex. Infusion of 0.25% acetic acid irritated the bladder, induced bladder overactivity and significantly decreased bladder capacity to about 20% of control capacity measured during saline infusion. Tibial nerve stimulation at low (5 Hz) or high (30 Hz) frequency significantly increased bladder capacity to about 40% of saline control capacity when it was applied during acetic acid infusion cystometrogram. Bladder contraction amplitude was smaller during acetic acid irritation than during saline distention due to significantly smaller bladder capacity. Tibial nerve stimulation at 5 Hz increased bladder capacity and bladder contraction amplitude. Activation of somatic afferents in the tibial nerve of cats can partially reverse the bladder overactivity induced by intravesical administration of a chemical irritant that activates C-fiber afferent nerves. These data are consistent with clinical studies showing that tibial nerve neuromodulation is effective treatment for overactive bladder symptoms.